Nanotechnology-enabled modulation of reactive oxygen species in cancer and chronic inflammation: a systematic review of therapeutic advances and translational challenges

Reactive oxygen species (ROS) are key regulators of cellular signalling and homeostasis, but if not managed, they can cause genomic instability, activation of carcinogenic pathways, and chronic inflammation. Approaches to ROS regulation using nanotechnology have demonstrated promise in preclinical models of inflammatory disorders and cancer but have yet to be transferred clinically due to concerns about specificity, safety, measurement, and standardization in redox regulation. The aim of this study was to assess nanotechnology strategies for achieving spatiotemporally controlled ROS modulation, highlighting technical challenges, safety issues, and translation barriers. We conducted a PRISMA 2020 systematic review (2013–2023) across PubMed, Scopus, and Web of Science. Eligible publications were screened using preset criteria; bias was assessed with SYRCLE. We synthesised nanomaterial classes, ROS-modulating mechanisms, therapeutic effects, and translational hurdles. We separately summarise findings for cancer and for chronic inflammation, then integrate convergences. Key findings include: ROS-induced genotoxic stress promotes malignant transformation and therapy resistance; persistent oxidative signalling enhances NF-κB/AP-1 activation and M1 polarisation, driving fibrosis and chronic inflammation. Harmonised procedures are necessary to address safety and standardisation issues, including chronic toxicity, immunogenicity, and inter-laboratory assay variation. Biomarker-stratified trials outperformed unstratified designs, and combination nanotherapies improved cancer cell kill over monotherapies. Nanotechnology-based ROS regulation is promising for cancer and chronic inflammatory illnesses but requires high-precision subcellular targeting, dual-threshold release, complete safety profiling, standardised ROS assays, and unified biomarker platforms for translation.